Probiotics are live microbes which, when administered to man or animals, promote the well being of the host by improving the intestinal microbial balance (Fuller, R. Probiotics in man and animals, 1989, J. Appl. Microbiol. 66:365-378). The best-documented probiotics include L. rhamnosus LGG, L. johnsonii LAI, L. casei Shirota and Bifidobacterium lactis Bbl2. In addition, a number of other probiotics have been described in the literature of the art (see for example M. E. Sanders & J. H. in't Veld 1999. Antonie van Leeuwenhoek 76:293-315, Kluwer Academic Publishers). The health-promoting effects of probiotics include the balancing and maintenance of intestinal flora, stimulation of the immune system and anti-carcinogenic activity. The useful effects of probiotics in human intestines are based on several factors caused by live bacterial cells, their cell structures and metabolic products. Probiotics are usually administered in nutrients or as capsules.
A bacterium may be referred to as a probiotic if it essentially meets the following requirements (Lee, Y-K and Salminen, S. 1995 The coming age of probiotics. Trend Food Sci Technol, 6:241-245): it remains viable in the demanding conditions prevailing in the digestive tract (low pH of the stomach, acids of the digestive system, etc.); attaches to the walls of the intestine; metabolizes in the intestine; is technologically applicable (endures processing); exhibits clinically tested and reported health effects; and is safe to consume.
Prebiotics are nondigestible food ingredients which promote the health of humans by selectively stimulating the growth and activity of one or some probiotic bacteria in the colon (Gibson, G. R. and Roberfroid, M. B. 1995. Dietary modulation of the human colonic microbiota—introducing a concept of prebiotics. J. Nutr. 125:1401-1412). A prebiotic is usually a nondigestible carbohydrate (oligo- or polysaccharide) or a sugar alcohol which is not degraded or absorbed in the upper digestive tract. Known prebiotics used in commercial products include inulin (fructo-oligosaccharide, or FOS) and transgalacto-oligosaccharides (GOS or TOS).
A synbiotic is defined as a combination of a prebiotic and a probiotic, the prebiotic promoting the viability of the added microbe and its attachment to the intestine, thereby promoting health (Gibson and Roberfroid 1995, supra). When nondigestible carbohydrates that have passed through the small intestine are fermented in the colon, short-chain fatty acids, other organic acids, alcohols, hydrogen and carbon dioxide, for example, are formed (Gibson and Roberfroid 1995, supra). The primary fatty acids produced in fermentation are acetic acid, butyric acid and propionic acid (Cummings, J. H. Short-chain fatty acids, in: Human Colonic Bacteria: Role in Nutrition, Physiology and Pathology, G. R. Gibson and G. T. Macfarlane (eds.), pp. 101-130, CRC Press, Boca Raton, 1995). An increase in the number of short-chain fatty acids would be generally advantageous. Nondigestible carbohydrates are the principal substrate for colonic microbes, although they also may include compounds the intestinal fermentation of which is disadvantageous (Gibson and Roberfroid, 1995, supra).
Human digestive tract accommodates a plural number of bacteria which live in symbiosis with the host. There are great differences in microbial content between the different parts of the tract, about 95% of all the intestinal bacteria appearing in the colon, which is the most important part of the intestines. Over 400 bacterial species have been estimated to thrive in the colon. In addition to these, the intestines contain microbes known as transient microbes (G. R. Gibson and M. B. Roberfroid (eds.) Colonic Microbiota; Nutirition and Health. Kluwer Academic Publisher, Dordrecht, 1999). The dominating species are the following: Bacteroides, Bifidobacterium, Coprococcus, Peptostreptococcus, Eubacterium and Ruminococcus. The number of species Lactobacillus, Streptococcus, Fusobacterium, Veillonella, Propionibacterium and Enterobacteriaceae is slightly less. Some of the species represent useful microbes, whereas others may even be harmful. The average microbial content in feces is 1012 cfu/g (per dry matter). Bacteria degrade and ferment those food ingredients in the colon, which are not absorbed in the small intestine, the end products of the fermentation being absorbed in the intestine for use by the body. In addition to nutrition, the microbial balance of the colon is of major significance to the state of health of a man (Tannock, G. W. 1998. Studies of the intestinal microflora: A prerequisite for the development of probiotics, Int. Dairy J. 8:527-533). Changes in the composition of the intestinal flora or a sudden reduction in the amount of it (due to severe diarrhea, antibiotics treatment, etc.) increase the infectivity of potentially pathogenic species, which may have serious consequences (outbreak of allergies, intestinal diseases, cancer).
The β-glucuronidase enzymes produced by intestinal bacteria are assumed to contribute to the formation of carcinogenic compounds, for example. Steroids and other carcinogenic compounds metabolize in the liver and then conjugate with glucuronic acid. The bile delivers the conjugated glucurone compound to the small intestine and from there the compound passes further to the colon where the glucuronidase enzymens can hydrolyse the compound, thereby releasing toxic compounds into the colon (Rowland, I. R. 1995. Toxicology of the colon: role of the intestinal microflora, in: Human Colonic Bacteria, Role in nutrition, physiology, and pathology. Editors: Gibson, G. R. and Macfarlane, G. T., pp. 155-174, Boca Raton: CRC Press). It is assumed that species of Eubacterium, Bacteroides and Clostridium release greater amounts of these harmful enzymes into the intestines than representatives of species of Bifidobacterium and Lactobacillus. This would thus provide one reason why it would be advantageous that the intestinal flora is composed of bifidobacteria and lactobacilli.
In addition, glycosides originating from vegetables and tea, for example, are not absorbed in the small intestine and pass to the colon, where they may be hydrolysed by the action of β-glucosidases to form toxic or mutagenic aglycone compounds (Goldin, B. R. 1990. Intestinal Microflora: metabolism of drugs and carcinogens. Annals of Medicine 22:43-48).
Moreover, the intestinal flora produces urease enzyme which degrades urea into ammonia. High amounts of ammonia may be toxic to the epithel cells of the intestine (Mobley, H. L. T. and Hausinger, R. P. 1989. Microbial ureases: significance, regulation and molecular characterization. Microbiological Reviews 53:85-108).
Human intestinal flora is formed during the early years of life and no major changes take place in its composition thereafter. Only minor changes within the species may take place (in bifidobacteria, for example).
Along with the increased understanding of the importance of intestinal flora, research has thus been actively focused on discovering the factors that can be used to influence the composition of the flora and its operation (viability) in such a way that beneficial bacterial species would be strengthened and harmful ones reduced. It is assumed that the operation of microbes can be influenced by prebiotics that promote beneficial bacteria. Extensive research has been carried out into galactooligosaccharides (GOS) which are di-, tri-, tetra-, penta- and hexasaccharides and which primarily contain galactose units. They are prepared enzymatically from lactose and the content of the end product depends on the enzyme used (Matsumoto, K. et al. 1993. Galactooligosaccharides, in: Oligosaccharides. Production, properties and applications. Ed. Nakakuki, T., Japanese Technology Reviews. Vol. 3. No. 2., pp. 90-116, Gordon and Breach Science Publishers, Switzerland, Australia). GOS has earlier been demonstrated to exhibit for example bifidogenic properties, i.e. those promoting the growth of bifidobacteria (Ito, M. et al. 1990. Effect of administration of galactooligosaccharides on the human faecal microflora, stool weight, and abdominal sensation. Microb. Ecol Health Dis. 3:285-292).